DNA腺嘌呤N6甲基化修饰在婴幼儿血管瘤发病机制中的作用

Role of N6-methyladenine DNA modification in the pathogenesis of infantile hemangioma

目的在表观遗传学层面研究DNA腺嘌呤N6甲基化(N6methyladenineDNA,6-mADNA)修饰是否与婴幼儿血管瘤的发生存在某些关系。方法通过MeDIP与高通量测序手段获得样本基因组的6-mADNA的数据,采用u检验对比3例增生期血管瘤瘤体标本与瘤旁皮肤组织中6-mADNA修饰水平,采用GO分析6-mA修饰基因的功能差异。结果瘤体组织中6-mADNA修饰水平较高,瘤体中6-mAPeaks在基因组上的覆盖度为O.037%,瘤旁皮肤组织中6-mAPeaks在基因组上的覆盖度为O.013%,两者比较差异有统计学意义(u=5999.87,P=O.OO)。瘤体中差异修饰的基因功能富集在中胚层发育、干细胞分化、间充质发育和细胞周期相关的功能的条目上,这些基因功能条目与血管瘤的发生密切相关。结论异常6-mADNA修饰可能是婴幼儿血管瘤的一项发病机制。

Objective To investigate whether N6-methyladenine DNA(6-mA DNA) modification is related to the occurrence of infantile hemangiomas (IH) at the epigenetic level.Methods The genomic 6-mA DNA data were obtained by MeDIP and high-throughput sequencing. The 6-mA DNA methylation levels in 3 proliferative hemangioma specimens and adjacent skin tissues were compared by u-test. The functional differences of 6-mA modified genes were analyzed by GO analysis.Results The level of 6-mA DNA modification in IH tissue was higher. The coverage of 6-mA Peaks in the genome was 0.037% in the tumor tissue, and the coverage of 6-mA Peaks in the surrounding skin tissue was 0.013% in the genome. The difference between the two groups was statistically significant (u=5999.87, P=0.00). The gene functions of differentially 6-mA modified genes in tumors were enriched in mesoderm development, stem cell differentiation, mesenchymal development, and cell cycle. These gene functions were closely related to the pathogenesis of IH.Conclusion Abnormal 6-mA DNA modification may be one of the pathogenesis of infantile hemangioma.